Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further evaluate the role of tryptophan and vitamin B6 in bladder carcinogenesis, male Fischer 344 rats were fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) in semipurified diet or were given semipurified diet alone for 4 weeks. One week later, rats from each group were assigned for the remainder of the experiment to one of four experimental diets, labeled as follows: group 1, control semipurified; group 2, L-tryptophan excess (2%); group 3, vitamin B6-deficient (1.0 mg/kg diet); or group 4, L-tryptophan excess, plus vitamin B6-deficient diet. All surviving rats were killed at 80 weeks of the experiment. Throughout the study, body weights were reduced in the groups fed FANFT and, at 70 and 80 weeks, body weights were reduced in the groups given tryptophan excess. The incidence of urinary bladder carcinoma was highest in the group treated with FANFT, followed by diet with control tryptophan and vitamin B6 levels (40%). The disease incidence was reduced in the vitamin B6-deficient group (13%) and of an intermediate range in the groups fed a tryptophan excess with or without vitamin B6 deficiency (28-29%). Tumors at other sites were greatest in number in FANFT-treated rats fed vitamin B6-deficient diet with excess tryptophan and were significantly fewer in FANFT-treated rats fed vitamin B6-deficient diet alone. Animals given diet deficient in vitamin B6 consistently had depressed levels of alanine aminotransferase activity and plasma pyridoxyl phosphate. FANFT pretreatment decreased alanine aminotransferase activities in rats in some groups and the feeding of tryptophan had variable effects on alanine aminotransferase and plasma pyridoxyl phosphate levels. Urinary tryptophan metabolites were influenced by all treatments, but the results did not correlate with tumor yields. Urinary bladder ornithine decarboxylase activity was not altered in vitamin B6-deficient female rats. These results do not support the hypothesis that increased dietary L-tryptophan promotes bladder carcinogenesis in rats, but other dietary factors might modify the process following FANFT initiation.
Cancer Res 1987 Mar 01
PMID:Effect of L-tryptophan excess and vitamin B6 deficiency on rat urinary bladder cancer promotion. 381 36

A series of multivariate analyses have been carried out in 49 patients with obstructive jaundice and three indices have been derived which help in the assessment of risk and the planning of investigation and management. The k-value, a measure of endogenous bilirubin clearance, is affected by cholangitis, alanine aminotransferase, pre-intervention bilirubin levels and the patient's sex. It has similar strength to the antipyrine clearance test in predicting morbidity and mortality. The mortality discriminant index is obtained from creatinine level, serum albumin and a score for cholangitis, and has an overall accuracy of 95%. The malignancy discriminant index depends on age, cholangitis score, creatinine level and gamma glutamyl transferase, and has an accuracy of 84%. All three indices have been programmed into a commercially available spreadsheet on a small microcomputer, and are automatically and rapidly available as soon as standard biochemical and clinical measurements have been entered.
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PMID:Use of a microcomputer in the assessment of diagnosis and risk in obstructive jaundice. 386 96

Clinical toxicities and pharmacokinetics of methotrexate (MTX), associated with reduced citrovorum factor (CF) neutralization, were studied on 279 infusions in 25 children with various malignancies. MTX, at 1000-8400 mg/m2, was infused during six to 24 hours with multiple schedules of reduced CF rescue. Plasma MTX levels ranged from 7.0 X 10(-5) to 7.0 X 10(-4) M during MTX infusion. The levels declined rapidly with a two-phase elimination pattern (t1/2 = 1.2-2.5 hours, t1/2 = 18-32 hours). The folate level in the plasma ranged from 5 X 10(-7) M to 1.4 X 10(-6) M when CF was administered every six hours or every three hours, respectively. Limited bone marrow suppression was seen in only seven percent of infusions, with moderate elevation of GOT and GPT in 20% of infusions, and stomatitis in only 2.6% of infusions, despite reduction in the total dose of CF from 225 mg to 105 mg and despite delaying CF initiation from nine hours to thirty-six hours after the start of MTX infusion.
Cancer Drug Deliv 1985
PMID:Reduced citrovorum factor rescue for high-dose methotrexate therapy in childhood malignancies. 387 73

A phase II study of recombinant interferon alpha A (Ro 22-8181) for malignant brain tumors was jointly conducted at 21 medical institutes in order to evaluate its clinical effects and side effects. Treatment started with exclusive administration of Ro 22-8181 at 3 X 10(6) U/day, which was increased appropriately after confirmation of its safety, until an optimum dose permitting long-term administration was achieved for each patient. The dose thus determined was intramuscularly administered daily. Among those treated, 39 patients were available for evaluation. The percentage of partial responses according to the "Criteria for the Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumor" by Koyama and Saito was 10.3% (4/39). Histologically, this was 7.1% (1/14) for glioblastoma and 14.3% (3/21) for malignant astrocytoma. Side effects included fever (57.3%), anorexia (34.1%), general fatigue (31.7%), leukopenia (52.4%) and thrombocytopenia (30.5%), and increased GOT and GPT (40.2%). In view of the success even in previously treated patients, and the side effects observed, Ro 22-8181 may be accepted as a useful addition to the treatment of malignant brain tumors.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in malignant brain tumors]. 388 62

A cooperative study was carried out in 32 institutions throughout the country to evaluate the clinical efficacy of recombinant human leukocyte A interferon (rIFN-alpha A, Ro 22-8181) on malignant tumors of the urogenital tract. The responses were evaluated according to the "Criteria for the Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumor" proposed by Koyama and Saito. Out of 269 cases which were examined in the present study, 138 cases were evaluable. Among 108 cases with renal cell carcinoma, efficacy was observed in 15 cases; complete response (CR) in 2 cases and partial response (PR) in 13 cases, indicating an efficacy rate of 13.9%. PR was obtained in 1 case out of 14 with bladder cancer and 1 case out of 6 with tumors of the renal pelvis and ureter. Main subjective and objective adverse reactions observed were fever, malaise, anorexia and nausea and/or vomiting. Laboratory test abnormalities consisted of leukopenia, thrombocytopenia and elevation of GOT X GPT. All of these disappeared with discontinuation of rIFN-alpha A or after administration of its therapeutic dose.
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PMID:[Clinical efficacy of recombinant human leukocyte A interferon (rIFN-alpha A) on malignant tumors of the urogenital tract]. 388 63

A Phase II study of recombinant leukocyte A interferon (rIFN-alpha A, Ro 22-8181) was performed in 121 patients with hematological malignancies at 33 institutions from July, 1982 to May, 1984. Patients received Ro 22-8181 by intramuscular injection daily for more than 4 weeks. Daily doses were escalated from 3 X 10(6) to 6X, 9X, 18X, 36X and 50X 10(6) units every 3-7 days. Among 70 evaluable cases, complete or partial responses were observed in 15 patients (21.4%). One complete and 10 partial responses (22.4%) were noted in 49 cases of multiple myeloma, 2 partial remissions (18.2%) in 11 cases of malignant lymphoma and 2 partial remissions (25.0%) in 8 cases of leukemia. Side effects included fever (57.0%), anorexia (34.2%), nausea-vomiting (22.8%), malaise (19.0%), leukopenia (44.3%), thrombocytopenia (45.6%) and increase of GOT or GPT (26.6% or 22.8%). They were all not serious and disappeared quickly after the discontinuation of Ro 22-8181.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in hematological malignancies]. 388 64

The pharmacokinetics of the new antifolate CB 3717 were studied in 20 patients during its phase-I clinical evaluation. The drug was administered at doses of 100-550 mg/m2 in 1-h and 12-h infusions, resulting in peak plasma concentrations of CB 3717 of 40-200 microM. There was a linear relationship between the dose and both CB 3717 AUC and peak plasma levels. Following a 1-h infusion, drug levels in the plasma decayed biphasically (t1/2 alpha = 49 +/- 9 min, t1/2 beta = 739 +/- 209 min). 27% +/- 2% of the dose was excreted in urine in the 24-h period after treatment, suggesting that the major route of elimination was via the bile. Furthermore, the parent compound CB 3717 and its desglutamyl metabolite, CB 3751, were found in a faecal collection although the metabolite was not detected in plasma or urine samples. Plasma protein binding of CB 3717 was extensive (97.6% +/- 0.1%). Significant quantities of CB 3717 penetrated into ascitic fluid but not into cerebrospinal fluid. Residual drug was detected in postmortem kidney tissue from a patient who died of progressive disease 8 days after treatment with 330 mg/m2 CB 3717. Thus, dose-limiting renal toxicity (maximum tolerated dose 600 mg/m2) may be due to drug precipitation in the renal tubules. Elevation of liver enzymes, in particular transaminases, occurred frequently as a toxic manifestation of CB 3717 therapy. In 11 patients studied after their first treatment there was a positive correlation between the rise in serum alanine transaminase and peak drug levels (r = 0.69, P = 0.02). These pharmacokinetic studies have shown that, by analogy with experimental systems, cytotoxic plasma levels of CB 3717 are archieved in man. In addition, they have been valuable in interpreting toxicities observed during phase-I clinical studies.
Cancer Chemother Pharmacol 1985
PMID:The clinical pharmacokinetics of the novel antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717). 399 86

A phase II study on recombinant human leukocyte A interferon (rIFN-alpha A) was carried out in 30 patients with urogenital cancers. Each patient received rIFN-alpha A by i.m. injection every day for at least 4 weeks. The initial daily dose was 3 X 10(6) U, being escalated at intervals of 3 days or more up to 50 X 10(6) U. The results are summarized as follows: In aged patients, the daily dose appropriate for everyday i.m. injection was considered to be 9 X 10(6) U or below, judging from the adverse reactions observed. According to Koyama and Saito's response criteria, partial response (PR) and minor response (MR) were obtained, respectively, in 3 and 1 out of 12 patients with renal cell carcinoma, while PR was seen in 1 out of 9 with urothelial cancer. No response was observed in patients with testicular cancer and in those with prostatic cancer. Various kinds of adverse reactions were recognized and each patient showed one reaction or more. Fever, fatigue, leukopenia, anemia, thrombocytopenia and elevation of GOT and GPT were observed relatively frequently. Among these, fatigue and thrombocytopenia were regarded as dose limiting factors.
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PMID:[Phase II study of recombinant human leukocyte A interferon on urogenital cancer patients]. 400 82

A study of C3H mice implanted with mammary tumours has shown that the levels of serum total protein, alanine transaminase and alkaline phosphatase are all lower than those found in normal mice, while aspartate transaminase is higher. Serum urea values were similar to normal levels, but creatinine was lower in males and higher in females. In the male mice, urine protein and urine N-acetyl-beta-D-glucosaminidase (NAG) activity were lower than in normal mice. Comparisons were made with age and sex matched controls which was found to be important for alkaline phosphatase, as this was shown to decrease with increasing age of the mice over the period from 10-30 weeks of age. The analyte values found in this study provide useful base-line data for assessing biochemical toxicity of cancer chemotherapy agents. It has been shown that some of these values can vary with age, or can be different if tumour-bearing mice are used instead of normal mice.
Br J Cancer 1985 Oct
PMID:The effect of C3H mouse mammary tumour on the levels of serum and urine analytes in vivo. 406 36

Alpha fetoprotein (AFP) was detected in sera (351 samples) of 128 patients with viral hepatitis by radioimmunoassay. 77 positive tests for AFP were obtained. These positive results were demonstrated on 1 or more samples taken from 40 (31%) of the 128 patients studied; the highest value obtained was 4400 ng/ml. Hepatitis B antigen (HBAg) was positive in 26/40 (65%) of patients in whom AFP was detected during the disease process. However, 58/88 (66%) who were seronegative for AFP also demonstrated HBAg in their sera. Chi-square analysis revealed no significant difference in occurrence of detectable AFP between HBAg seropositive and seronegative patients. Individuals seropositive for AFP had no statistically different concentration of the protein than patients seropositive or seronegative for HBAg. 24 patients' sera were tested serially over a 2-week period. Both the peak glutamic-pyruvic transaminase (GPT) and peak total bilirubin levels were in a higher range in those 10/24 patients seropositive (P .001) for AFP than in the 14/24 who were seronegative. Appearance of AFP was related to the severity of liver tissue destruction, as reflected by serum GPT. However, peak AFP levels were attained 5-16 days after peak serum GPT appeared in the circulation.
Cancer Res 1974 Jan
PMID:The detection of alpha 1-fetoprotein in patients with viral hepatitis. 480 61


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